The goal of the proposed studies and structured educational plan is to develop the PI into an independent investigator with the career goal of preventing acute complications and improving emergent management of sickle cell disease (SCD), with focus on learning innovative approaches to trial design to meet challenges specific to SCD research. The Principal Investigator will receive advanced individualized and classroom training that will build upon the candidate's strengths as an emergency physician and prior training in clinical investigation to learn specific quantitative skills necessary to transition ito the next phase of his career, including adaptive trial design methods, Bayesian analysis and longitudinal modeling techniques. SCD is an inherited disorder of hemoglobin with manifestations in all organ systems. One of the greatest risk factors for vaso-occlusion and death in adolescents and adults with SCD is the presence of respiratory symptoms such as cough or wheeze. Preliminary data indicate that recurrent cough or wheeze occurs in nearly half of individuals with SCD who do not carry a physician diagnosis of asthma. The proposed research is designed to test the global hypothesis that inhaled corticosteroids (ICS), a therapy developed to treat asthma, will prevent vaso-occlusive painful episodes in adults with SCD who wheeze, but do not meet criteria for a diagnosis of asthma. The specific aims of this proposal are 1) Conduct a feasibility study - a randomized controlled trial of ICS for adults with SCD who do not meet criteria for a diagnosis of asthma but report recurrent cough or wheezing, 2) Measure the effects of ICS on biological correlates of pulmonary inflammation (as determined by exhaled nitric oxide) and vascular injury (as determined by sVCAM) in SCD, and 3) Compare properties of traditional and Bayesian adaptive clinical trial design for therapeutic trials in SCD in preparation for designing a definitive trial of ICS. These aims have the potentia to 1) change the standard of care for individuals with SCD and recurrent cough or wheeze, 2) provide insight into the pathogenesis of non-asthmatic wheezing in SCD and its response to treatment, 3) explore the suitability of innovative clinical trial designs to overcome the challenges that have hindered therapeutic innovation for SCD.